Clinical and pathological manifestations of human henipavirus infection.

The clinicopathological features of human Nipah virus and Hendra virus infections appear to be similar. The clinical manifestations may be mild, but if severe, includes acute encephalitic and pulmonary syndromes with a high mortality. The pathological features in human acute henipavirus infections comprise vasculopathy (vasculitis, endothelial multinucleated syncytia, thrombosis), microinfarcts and parenchymal cell infection in the central nervous system, lung, kidney and other major organs. Viral inclusions, antigens, nucleocapsids and RNA are readily demonstrated in blood vessel wall and numerous types of parenchymal cells. Relapsing henipavirus encephalitis is a rare complication reported in less than 10% of survivors of the acute infection and appears to be distinct from the acute encephalitic syndrome. Pathological evidence suggests viral recrudescence confined to the central nervous system as the cause.

Periodic lateralized epileptiform discharges (PLEDs) in cerebral lupus correlated with white-matter lesions in brain MRI and reduced cerebral blood flow in SPECT.

This is a case report on an uncommon correlation between periodic lateralized epileptiform discharges (PLEDs) and white-matter lesions in cerebral lupus, and with a reduced cerebral blood flow (CBF) in single-photon emission computed tomography (SPECT). A 47-year-old woman with a long-term history of systemic lupus erythematosus (SLE) presented with a seizure followed by frontal lobe dysfunction clinically. An electroencephalogram (EEG) showed bilateral independent PLEDs in the frontal region. A magnetic resonance image of the brain showed white-matter changes in the frontal periventricular region. Cerebral angiogram did not reveal any evidence of vasculitis. A cerebral SPECT with tracer injected during the EEG showing PLEDs showed a reduction in CBF in the frontal regions. Clinical recovery was observed with intravenous immunoglobulin. This case shows that PLEDs can be seen with white-matter changes in SLE.

Adipokines and the risk of active TB: a nested case-control study.

BACKGROUND: Adipokines are emerging mediators of immune response, and may affect susceptibility to active TB.OBJECTIVE: To examine the associations between adipokines and the risk of active TB.METHODS: In a case-control study nested within a prospective cohort of middle-aged and older adults in Singapore, 280 incident active TB cases who donated blood for research before diagnosis were matched with 280 controls. Serum levels of adiponectin, resistin, leptin and ghrelin were measured. Multivariable logistic regression models were used to compute the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between adipokines and the risk of active TB.RESULTS: Higher levels of leptin and resistin were associated with reduced risk of TB in a dose-dependent manner. Compared to those in the lowest quartile of leptin levels, those in the highest quartile had an OR of 0.46 (95%CI 0.26-0.82; P for trend = 0.009). Similarly, compared to those in the lowest quartile of resistin levels, those in the highest quartile had an OR of 0.46 (95%CI 0.24-0.90; P for trend = 0.03). Adiponectin and ghrelin levels were not associated with TB risk.CONCLUSION: Increased serum levels of leptin and resistin may be associated with reduced susceptibility to active TB infection.

Periodic lateralized epileptiform discharges in neuropsychiatric lupus: association with cerebritis in magnetic resonance imaging and resolution after intravenous immunoglobulin.

A 13-year-old girl with a known diagnosis of systemic lupus erythematosus presented with seizures and psychosis. An electroencephalogram (EEG) revealed continuous, non-evolving periodic lateralized epileptiform discharges (PLEDs) in the left temporal region, which did not resolve with benzodiazepine. A magnetic resonance imaging (MRI) brain scan demonstrated a focal hyperintensity in the left medial temporal and left occipital lobes, left thalamus and bilateral cerebellar white matter, with evidence of vasculitis in the magnetic resonance angiography. Intravenous immunoglobulin was given because of failed steroid therapy, which resulted in a full resolution of clinical, EEG and MRI abnormalities. Lupus cerebritis should be considered as a possible aetiology in PLEDs, and immunoglobulin can be effective in neuropsychiatric lupus.

Bulbar signs in normal population.

BACKGROUND AND OBJECTIVES: There is lack of published data on bulbar signs among the healthy population. This study aims to determine the range of normality of bulbar signs particularly among the elderly. METHODS: Systemic examination of bulbar signs was carried out according to a predetermined protocol on a cohort of young and elderly healthy subjects. RESULTS: A total of 206 subjects were recruited in the study, 104 young adults with mean age of 20 years, and 102 elderly with mean age of 73 years. Uvula deviation was seen in 28 (26.9%) young subjects and 22 (21.6%) elderly. Irregular tongue border was seen in 17 subjects, unilateral in 4 subjects. Fourteen (6.8%) subjects had deviation on tongue protrusion. Occasional tremor of tongue on protrusion is common in both young and old. Persistent (severe) tongue tremor on protrusion was seen in 18.6% of the elderly, and 4.8% of the young. None of the subjects had tremor of tongue at rest. In gag reflex, absence of gagging response was common in elderly, seen in two thirds of the subjects on stimulation of the posterior pharyngeal wall. However, all the subjects had uvular movement. Habituation or suppression of gagging response was seen in close to 90% of young males. CONCLUSION: There is wide range of normality in bulbar signs in normal population, particularly among the elderly.

Involvement of matrix metalloproteinase-13 in stromal-cell-derived factor 1 alpha-directed invasion of human basal cell carcinoma cells.

Basal cell carcinoma (BCC) is one of the most common skin neoplasms in humans and is usually characterized by local aggressiveness with little metastatic potential, although deep invasion, recurrence, and regional and distant metastases may occur. Here, we studied the mechanism of BCC invasion. We found that human BCC tissues and a BCC cell line had significant expression of CXCR4, which was higher in invasive than non-invasive BCC types. Further, of 19 recurrent tumors among 390 BCCs diagnosed during the past 12 years, 17/19 (89.5%) had high CXCR4 expression. We found that the CXCR4 ligand, stromal-cell-derived factor 1alpha (SDF-1alpha), directed BCC invasion and that this was mediated by time-dependent upregulation of mRNA expression and gelatinase activity of matrix metalloproteinase-13 (MMP-13). The transcriptional regulation of MMP-13 by SDF-1alpha was mediated by phosphorylation of extracellular signal-related kinase 1/2 and activation of the AP-1 component c-Jun. Finally, CXCR4-transfected BCC cells injected into nude mice induced aggressive BCCs that co-expressed CXCR4 and MMP-13. The identification of SDF-1alpha/CXCR4 as an important factor in BCC invasiveness may contribute insight into mechanisms involved in the aggressive potential of human BCC and may improve therapy for invasive BCCs.

Diagnostic utility of F waves in cervical radiculopathy: electrophysiological and magnetic resonance imaging correlation.

OBJECTIVE: F wave study is a simple, non-invasive method commonly utilized for evaluation of cervical root lesions. Its diagnostic sensitivity is low. There are no large series comparing F wave studies with MRI as a reference standard. PATIENTS AND METHODS: We performed F wave studies in 30 controls (15 men; mean age: 50 years; standard deviation: 17.9 years; range: 21-80 years) and, prospectively, 31 patients (19 men; mean age: 48 years; standard deviation: 16.2 years; range: 26-79 years) referred for evaluation of cervical spondylotic radiculopathy (CSR). All patients' MRIs were compared with F wave parameters. RESULTS: Combined utilization of minimal F latency, F chronodispersion, F persistence and side to side differences resulted in 55% sensitivity and 100% side concordance for detecting CSR, with MRI as a comparison standard. F wave parameters also provided complementary information to needle electromyography in the diagnostic evaluation of CSR. Although F waves were not indicative of radiculopathy levels, 4/31 (13%) of cases had at least one abnormal F wave parameter, despite normal electromyography findings. CONCLUSIONS: Combined utilization of multiple F wave parameters is a useful, diagnostic adjunct in the electrophysiological evaluation of CSR.

A review of multiple sclerosis with Asian perspective.

Multiple sclerosis, although a rare disease in Asia, often presents significant diagnostic challenges to clinicians. There has been rapid advancement in the understanding of the underlying genetic influence, pathophysiology, investigation and treatment recently. This paper reviewed the latest development of various aspects of the disease and examined the differences between the manifestations of Asian and Western patients. The implications of these differences to investigation and treatment were also touched upon.

Cutaneous silent periods in the evaluation of cord compression in cervical spondylosis.

OBJECTIVE: The clinical diagnosis of cervical spondylotic myelopathy (CSM) may be challenging in patients with cervical spondylosis (CS). Routine nerve conduction studies (NCS) may not evaluate cord compression adequately. METHODS: We obtained cutaneous silent periods (CSP) in 26 consecutive patients presenting with clinical features of CS, in comparison with 30 normal controls. The results were also compared with transcranial magnetic stimulation (TMS) findings, and magnetic resonance imaging of the cervical cord as the gold standard. RESULTS: CSP findings showed similarly high sensitivity of up to 96% with TMS in evaluating cervical cord dysfunction. CONCLUSION: In specific clinical settings, CSP is of value for the diagnosis of CSM in CS. CSP measurement is advocated as a simple and rapid diagnostic adjunct to NCS in evaluating CS patients with possible cord compromise.

The Prevalence of Anti-Aquaporin 4 Antibody in Patients with Idiopathic Inflammatory Demyelinating Diseases Presented to a Tertiary Hospital in Malaysia: Presentation and Prognosis.

Background. There have been inconsistent reports on the prevalence and pathogenicity of anti-Aquaporin 4 (AQP4) in patients presented with idiopathic inflammatory demyelinating diseases (IIDDs). Objective. To estimate the prevalence of anti-AQP4 antibody in patients with IIDDs presented to University Malaya Medical Centre in terms of patients' clinical and radiological presentations and prognoses. Methods. Retrospective data review of IIDDs patients presented from 2005 to 2015. Patients were classified into classical multiple sclerosis (CMS), opticospinal (OS) presentation, optic neuritis (ON), transverse myelitis (TM), brainstem syndrome (BS), and tumefactive MS. Anti-Aquaporin 4 antibody was tested using the Indirect Immunofluorescence Test (IIFT) cell-based assay. Statistical analysis was done using the SPSS version 20. Results. Anti-AQP4 antibody was detected in 53% of patients presented with IIDDs. CMS was more common in the seronegative group, 27/47 (57.45%; p < 0.001). Conversely, OS involvement was more common in the seropositive group, 26/53 (49.06%; p < 0.001). Longitudinally extensive spinal cord lesions (LESCLs) on MRI were also more common in the seropositive group, 29/40 (72.50%; p = 0.004). Only 2/40 (5.00%) had MRI evidence of patchy or multiple short-segment spinal cord lesions in the AQP4-positive group (p = 0.003). The relapse rate and Expanded Disability Status Scale (EDSS) were also higher in the seropositive group (5.43 versus 3.17, p = 0.005; 4.07 versus 2.51, p = 0.006, resp.). Typical clinical presentations that defined NMO were also seen in the seronegative patients, but in a lower frequency. Conclusion. Our cohort of patients had a higher prevalence of seropositivity of anti-AQP4 antibody as compared to those in Western countries. This was also associated with a more typical presentation of opticospinal involvement with LESCLs on MRI, a higher rate of relapse, and EDSS.

B-cell lymphoma/leukemia 10 promotes oral cancer progression through STAT1/ATF4/S100P signaling pathway.

This corrects the article DOI: 10.1038/onc.2014.43.

Transcranial magnetic stimulation screening for cord compression in cervical spondylosis.

OBJECTIVE: Cervical spondylosis (CS) often results in various degrees of cord compression, which can be evaluated functionally with transcranial magnetic stimulation (TMS). We investigate the use of TMS as a screening tool for myelopathy in CS. METHODS: We prospectively studied 231 patients classified into Groups 1 to 4 based on MRI grading of severity of cord compromise. TMS elicited central motor conduction times and motor evoked potential (MEP) amplitudes in all 4 limbs. The results were compared with those from 45 healthy controls. RESULTS: TMS showed 98% sensitivity and 98% specificity for cord abnormality using MRI as reference standard. CONCLUSIONS: MEP abnormalities are useful for electrophysiological evaluation of cord compression in CS. While TMS is not a substitute for MRI, it is of value as a rapid, inexpensive and non-invasive technique for screening patients before MRI studies.

Magnetic resonance imaging of Asians with multiple sclerosis was similar to that of the West.

Magnetic resonance imaging (MRI) of the brain is the most important paraclinical diagnostic test in multiple sclerosis (MS). The appearance of MRI in Asians with MS is not well defined. We retrospectively surveyed the first brain and spinal cord MRI in patients diagnosed to have MS, according to Poser's criteria in seven regions throughout Asia to define the MRI changes among Asians with MS. There were 101 patients with first brain, and 86 with first spinal cord MRI, 66 of whom had both. The brain MRI showed a mean of 17 lesions per patient in T2 weighted images, mostly asymptomatic. Almost all the lesions were in the white matter, particularly in the juxtacortical, deep and periventricular white matter. A third of the lesions were greater than 5 mm, 14% enhanced with gadolinium. There were more supratentorial than infratentorial lesions at a ratio of 7.5: 1. Ninety five percent of the spinal cord lesions were in cervical and thoracic regions, 34% enhanced with gadolinium. The lesions extended over a mean of 3.6 +/- 3.3 vertebral bodies in length. Fifty (50%) of the brain and 54 (63%) of the spinal MRI patients had the optic-spinal form of MS. The MRI of the optic-spinal and classical groups of patients were similar in appearance and distribution, except that the optic-spinal MS patients have fewer brain but longer and more severe spinal cord lesions. In conclusion, the brain and spinal cord MRI of Asian patients with MS was similar to that of the West, although, in this study, Asian MS patients had larger spinal cord lesions.

Intraoperative monitoring study of ipsilateral motor evoked potentials in scoliosis surgery.

Ipsilateral motor evoked potentials (MEPs) in spinal cord surgery intraoperative monitoring is not well studied. We show that ipsilateral MEPs have significantly larger amplitudes and were elicited with lower stimulation intensities than contralateral MEPs. The possible underlying mechanisms are discussed based on current knowledge of corticospinal pathways. Ipsilateral MEPs may provide additional information on the integrity of descending motor tracts during spinal surgery monitoring.

Incidence of second cancers in patients treated for Hodgkin's disease.

BACKGROUND: Numerous studies of treatment for Hodgkin's disease have demonstrated large increases in the incidence of leukemia in the early years following chemotherapy, although the duration of effect and the specific agents involved are not well understood. Also, some, but not all, studies have indicated that the incidence of certain solid tumors increases following treatment for Hodgkin's disease. PURPOSE: We studied the association between treatment for Hodgkin's disease and the incidence of second cancers. METHODS: We conducted a study within a cohort that included 10,472 patients from 14 cancer centers in the United States and Canada who were first diagnosed as having Hodgkin's disease at some point from 1940 through 1987. Discounting the 1st year after diagnosis, the average length of follow-up was 7.1 years per subject. RESULTS: We observed 122 leukemias and 438 solid tumors. The relative risk (RR) of leukemia following chemotherapy, compared with no chemotherapy, was 14 (95% confidence interval [CI] = 5.6-35). Increased risks of leukemia were observed after treatment with chlorambucil (RR = 2.0; 95% CI = 1.1-3.6), procarbazine (RR = 4.9; 95% CI = 2.6-9.1), vinblastine (RR = 1.7; 95% CI = 1.1-2.8), and a group of rarely used drugs that included methotrexate, vindesine, etoposide, and 22 others (RR = 3.8; 95% CI = 1.9-7.4). RRs were also estimated for various combinations of drugs, including MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) (RR = 5.9; 95% CI = 2.9-12) and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) (RR = 1.5; 95% CI = 0.7-3.4). The RR of leukemia associated with splenectomy was 1.6 (95% CI = 1.0-2.5). The RR of solid tumors following chemotherapy was 1.4 (95% CI = 1.1-1.8). For the group of rarely used drugs, the RR of solid tumors was 3.1 (95% CI = 1.7-5.8). Chemotherapy was associated with an increased risk of cancers of the bones, joints, articular cartilage, and soft tissues (RR = 6.0; 95% CI = 1.7-20), and cancers of the female genital system (RR = 1.8; 95% CI = 1.1-3.2). In patients followed for 10 or more years after radiotherapy, increased risks were found for cancers of the respiratory system and intrathoracic organs (RR = 2.7; 95% CI = 1.1-6.8) and for cancers of the female genital system (RR = 2.4; 95% CI = 1.1-5.4). CONCLUSIONS: Procarbazine, chlorambucil, and vinblastine are associated with increased leukemia risk. Combination drug regimens have leukemogenic effects estimated as the product of RRs for individual drugs. Chemotherapy and radiotherapy increase the risk of selected solid tumors, and the effect of chemotherapy on solid tumor risk is weaker than the leukemogenic effect. IMPLICATIONS: Without doubt, the benefits of treatment of Hodgkin's disease outweigh the risk of a subsequent malignancy, but data on the carcinogenic effects of radiation and drugs beyond 10 years after treatment continue to be sparse, and future analyses should be directed at long-term survivors.

Phase I study of aziridinylbenzoquinone (AZQ, NSC 182986) in children with cancer.

Aziridinylbenzoquinone is a quinone compound capable of penetrating the central nervous system. It has demonstrated activity against both intracranial and i.p. murine tumors and human tumor xenographs. We have conducted a Phase I trial of aziridinylbenzoquinone in 60 children with advanced cancer who were refractory to conventional therapy. The drug was given by slow i.v. push on a daily schedule for 5 days every 3 to 4 weeks. The dose range explored included 6 dose levels, ranging from 6 to 12 mg/sq m daily for 5 days in patients with solid tumors and leukemia, and in patients with leukemia, 20, 25, and 30 mg/sq m daily for 5 days. Myelosuppression was the dose-limiting side effect. In patients with solid tumor the highest dose studied was 12 mg/sq m, and the median nadir white blood cell and platelet counts were 0.7 X 10(3) and 6.0 X 10(3)/microliter on Days 17 and 22, respectively. The median recovery day for white blood cells was 39. There may be some evidence of cumulative toxicity with prolonged thrombocytopenia. Other side effects were mild nausea, vomiting, and mucositis. Elevations in liver enzymes and bilirubin were transient and dose dependent, occurring 3 to 4 weeks after drug administration. Of the 34 children with solid tumors, 33 were evaluable for hematopoietic toxicity, 3 were early deaths, and 31 receiving a total of 55 courses were evaluable for therapeutic response. Partial responses lasting 3 weeks to 6 months were seen in the 4 patients with Hodgkin's disease, and in a child with a metastatic spinal cord ependymoma. Fifty-two courses were given to 9 patients with acute lymphocytic leukemia and 17 with acute nonlymphoblastic leukemia. Of the 15 patients with acute nonlymphoblastic leukemia treated at doses greater than or equal to 25 mg/sq m/day for 5 days there was one early death and there were 2 M1 (less than or equal to 5% blasts with normal cellularity), 3 M2A (6 to 15% blasts), and 2 M2B (16 to 39% blasts) bone marrow responses lasting 1 to 3.5 months. Aziridinylbenzoquinone demonstrated activity against acute nonlymphocytic leukemia with maximal tolerated doses of 30 mg/sq m daily for 5 days. Its effect in Hodgkin's disease is encouraging; however, further study will be required to determine its efficacy in central nervous system cancers. Recommended doses for Phase II studies, using daily schedule for 5 days in children with solid tumors, is 9 mg/sq m, and in children with leukemia, it is 25 mg/sq m.

In vitro responses of peripheral blood and spleen lymphoid cells to mitogens and antigens in childhood Hodgkin's disease.

Over the past 5 years, parameters of immunological function have been determined in all children with biopsy-proven Hodgkin's disease in the Department of Pediatrics, Memorial Sloan-Kettering Cancer Center. This report summarizes the in vitro responses of lymphocytes to stimulation by mitogens and antigens (between January 1975 and December 1976) in 33 of these previously untreated patients. In nine of these patients, responses of the splenic lymphocytes were studied concomitantly with the responses of peripheral blood lymphocytes. Peripheral blood from normal children and adults was used as the control. Our results have demonstrated no significant differences between the responses of normal children and adult controls. The absolute necessity for concomitant studies of the controls and the patients was shown. The value of examining multiple concentrations of a single mitogen was also well defined. In the children with Hodgkin's disease, there was a consistent failure of the peripheral blood lymphocytes to respond to the lower concentration dose of phytohemagglutinin. However, this abnormality was not found in the splenic lymphocytes.

Treatment of acute lymphoblastic leukemia in childreq with "prophylactic" intrathecal methotrexate and intensive systemic chemotherapy.

Sventy-five children under the age of 15 years, with acute lymphoblastic leukemia, were treated with a multiple drug chemotherapy regimen (L-2) and intrathecal methodtrexate. Remission was achieved in all except 1. Three died from infection early in remission and 1 was lost to follow-up. Of the remaining 70, relapse occurred in 19; in 3 children this was confined to the central nervous system (CNS) and in 1 was in both the CNS and bone marrow. Fifty-one children continue in complete remission from 14 to 54 months. Fourteen of these children have completed 3 years of chemotherapy and are disease free 2 to 18 months posttreatment. The results indicate that periodic administration on intrathecal methotrexate with no CNA irradiation, plus intensive systemic chemotherapy, can effectively control CNA leukemia and prolong the duration of complete remissions.